2-benzoyl -3-amino-pyridines

ABSTRACT

WHERE R1 is halogen, R2 and R3 are hydrogen, halogen, trifluoromethyl, hydroxy, cyano, lower alkyl or lower alkoxy, R4 is hydrogen or lower alkyl, and R5 is hydrogen, lower alkyl, benzoyl, substituted benzoyl, lower carbalkoxy or There are prepared compounds of the formula WHERE A is oxygen, sulfur, imino or lower alkylimino and R6 is lower alkyl, lower alkyl having 1 to 3 halogen atoms, lower alkenyl, hydroxymethyl, carboxymethyl, carb-lower alkoxy methyl, amino lower alkyl or alkylaminoalkyl having 2 to 13 carbon atoms or where any hydroxy or primary or secondary amino group is substituted by an alkanoyl group of 2 to 8 carbon atoms, carbalkoxy having 1 to 6 carbon atoms, carbophenoxy or carbobenzyloxy or a pharmacologically acceptable salt thereof. The compounds are useful in emotional disturbances, tension, anxiety, increased irritability.

United States Patent n 1 Von Bebenburg et al.

[451 Apr. 1, 1975 Z-BENZOYL -3-AMlNO-PYRIDINES [75] Inventors: WalterVon Bebenburg.

Buschschlag; Herihert Oifermanns. Grossauheim. both of Germany [22]Filed: Apr. 3, 1973 [2]] Appl. No: 347,361

[30] Foreign Application Priority Data May 10. 1972 Austria A 4113/72[56] References Cited UNITED STATES PATENTS 10/1973 Sulkowski 260/296 R12/1973 Topliss 260/570 AB OTHER PU BLlCATlONS Hromatka et al., Chem.Abstracts. Vol. 71, (23) l12.995(a) Dec.8. 1969.

Primary E.\'aminerAlan L. Rotman Attorney, Agent. or Firm-Cushman. Darby& Cushman [57] ABSTRACT There are prepared compounds of the formula Ru l5 where R is halogen. R and R are hydrogen. halogen. trifluoromethyl.hydroxy, cyano. lower alkyl or lower alkoxy. R is hydrogen or loweralkyl. and R is hydrogen. lower alkyl. benzoyl. substituted benzoyl.lower carbalkoxy 0r where A is oxygen. sulfur. imino or lower alkyliminoand R is lower al-kyl. lower alkyl having 1 to 3 halogen atoms. loweralkenyl, hydroxymethyl. carboxymethyl, carb-lower alkoxy methyl. aminolower alkyl or alkylaminoalkyl having 2 to 13 carbon atoms or where anyhydroxy or primary or secondary amino group is substituted by analkanoyl group of 2 to 8 carbon atoms. carbalkoxy having 1 to 6 carbonatoms. carbophenoxy or carbobenzyloxy or a pharmacologically acceptablesalt thereof. The compounds are useful in emotional disturbances.tension, anxiety. increased irritability.

11 Claims, N0 Drawings 2-BENZOYL-S-AMINO-PYRIDINES The invention isdirected to the product of compounds of the formula t ll where R, ishalogen, e.g. chlorine, bromine or fluorine, R and R are hydrogen, e.g.fluorine, chlorine or bromine, trifluoromethyl, hydroxy, cyano, loweralkyl, e.g.

A ll

6 where A is oxygen, sulfur, imino or lower alkylimino, e.g. with l to 7carbon atoms and R is lower alkyl, e.g. of l to 7 carbon atoms, loweralkyl having 1 to 3 halogen atoms, e.g. alkyl of l to 7 carbon atomswherein the halogens are chlorine, bromine or fluorine, lower alkenyl,e.g. with 2 to 7 carbon atoms, hydroxymethyl, carboxymethyl, carb-loweralkoxy methyl, e.g. with l to 7 carbon atoms, amino lower alkyl, e.g.with l to 7 carbon atoms, or alkylaminoalkyl having 2 to 13 carbon atomsor where any hydroxy or primary or secondary amino group is substitutedby an alkanoyl group of 2 to 8 carbon atoms, carbalkoxy having 1 to 6carbon atoms, carbophenoxy or carbobenzyloxy or a pharmacologicallyaccepted salt thereof.

As halogens there are employed chlorine, fluorine and bromine, i.e.halogens of atomic weight 9 to 80, especially chlorine and bromine. Inthe above named lower alkyl. alkenyl, alkylamino, alkoxy, alkylimino,alkanoyl and carbalkoxy groups preferably there are present 1 to 6carbon atoms (2 to 6 carbon atoms for the alkenyl group), especially 1to 4 carbon atoms (2 to 4 carbon atoms for the alkenyl group). (This isalso true if these groups are present in the compound with a furtherchemical redical designation such as for example, carbalkoxymethyl andaminoalkyl). These groups, especially the alkyl and alkenyl groups canbe straight or branched chain. The substituted benzoyl group (R) issubstituted in the phenyl nucleus with one to three (0, m, orppositions) halogen atoms, especially chlorine, bromine or fluorineand/or lower alkyl, e.g. with l to 6 carbon atoms, especially 1 to 4carbon atoms (for example methyl). Preferably, the substituents are inthe oand ppositions. The halogen substituted alkyl groups can have 2 or3 halogen atoms, for example, fluorine atoms or the same carbon atoms asis the case for example with the trifluoroacetyl group.

An especially preferred group of compounds within formula I is thatwherein R, is chlorine, R is hydrogen or halogen, R is hydrogen, R ishydrogen or alkyl with l to 3 carbon atoms and R is hydrogen or analiphatic acyl group of 2 to 4 carbon atoms or an aliphaticallyunsaturated acyl group with 3 to 5 carbon atoms, (e.g.

ethylenically unsaturated), a haloacetyl group, an aminoacetyl group, acarbmethoxy group, a carbethoxy group or a benzoyl group.

Even more preferred are compounds of formula I where R is chlorine, R ishydrogen, chlorine or fluorine, R is hydrogen, R, is hydrogen or methyl,R is bydrogoen, acetyl, propionyl, chloroacetyl, bromoacetyl oraminoacetyl.

In addition to the compounds mentioned in the specific working examples,there can also be made by the same procedures other compounds within theinvention such as 2-benzoyl-3-amino-6-fluoropyridine, 2-benzoyl-3-amin'o-6-bromo-pyridine, 2-benzoyl-3-(3,3-

dimethyl-acryloxylamino )-6-bromopyridine, 2-benzoyl-3-benzoylamino-6-fluoro-pyridine, 2-( pchlorobenzoyl)-3-amino-6-chloro-pyridine, 2-( mchlorobenzoyl)-3-amino-6-chloropyridine, 2-(obromobenzoyl)-3-amino-o-chloropyridine,2-( pbromobenzoyl )-3-amino-6-bromo-pyridine, 2-(0-fluorobenzoyl)-3-amino-6-fluoro-pyridine, 2-( ochlorobenzoyl)-3-methylamino)-6-chloropyridine, 2-benzoyl-3-chloroacetylamino-6-chloro-pyridine, 2-benzoyl-3-bromoacetyl-amino-6-chloro-pyridine, 2-benzoyl-3-ethylamino-6-chloropyridine, 2-(ochlorobenzyol)-3-isopropylamino-6-chloro-pyridine,

2-benzoyl-3-n-propylamino-6-bromopyridine, 2-

benzoyl-3-butyrylamino-6-chloropyridine, Z-benzoyl-3-acryloylamino-6-chloropyridine, 2-benzoyl-3- (methacryloylethylamino)-6-chloro-pyridine, 2-benzoyl-3-carbmethoxyamino-6-chloro-pyridine, 2-

benzoyl-3-carbethoxy-methylamino,-6-chloropyridine2-(o-trifluoromethyl-benzoyl)-3-amino-6-chloropyridine,2-(o-methyl-benzoly)-3-amino-6-chloropyridine,2-(p-ethylbenzoyl)-3-amino-6- chloropyridine, 2-(2,4'-dimethylbenzoyl)-3-amino-6- bromo-pyridine,2-(2'-chloro-4-methyl-benzoyl)-3- amino-6-chloropyridine,2-(o-butylbenzoyl)3-amino-6- chloropyridine,2-(p-hexylbenzoyl)-3-amino-6- chloropyridine,2-(o-hydroxybenzoyl)'3-amino-6- chloropyridine,2-(p-hydroxy-benzoyl)-3-acetylamino- 6-chloro-pyridine, 2-(2,4-dihydroxybenzoyl)-3- amino-6-chloropyridine,2-(o-cyanobenzoyl)-3-amino- 6-chloropyridine, 2-(m-cyano-benzoyl)-3-methylamino-6-chloropyridine, 2-benzoyl-3-trifluoroacetyl-amino-6-chloropyridine, 2-benzoyl-3-carbophenoxyamino-6-chloro-pyridine, 2-benzoyl-3-carboamyloxy-6-chloropyridine,2-benzoyl-3-(betachloropropionyl-amino-6-chloropyridine, 2-benzoyl-3-dihexylamino-6-chloropyridine,2-benzoyl-3-thiopropionylamino--chloropyridine, 2-benzoyl-3-thiocarbethoxy-amino-6-chloropyridine, 2-(ochlorobenzoyl)-3-thiobenzoylamino-6-chloropyridine, 2-(p-chlorobenzoyl)-3-thioacetamino-6- chloropyridine, 2-(o-chloro-benzoyl)-3-benzyloxythiocarbonylaminoacetamino-6- chloropyridine, 2-benzoyl-3-(2-chloroacryloylamino )-6-chloropyridine, 2-benzoyl-3-ethyliminoamino-6-chloropyridine, 2-benzoyl-3- propyl(methyl)iminoamino-6-chloropyridine, 2--

benzoyl-3-iminocarbethoxyamino-6-chloropyridine,2-(o-methoxybenzoyl)-3-amino-6-chloropyridine,2(pethoxybenzoyl)-3-methylamino-6-chloropyridine.

There can be prepared and used the salts with pharmacologicallyacceptable acids such as hydrochloric acid, hydrobromic acid, succinicacid, tartaric acid, fumaric acid, sulfuric acid, citric acid,phosphoric acid,

lactic acid, malonic acid, maleic acid, acetic acid, propionic acid andp-toluenesulfonic acid.

The compounds of the invention have valuable pharmacodynamic properties.Especially they have marked sedative, psychosedative and anxiolyticproperties as well as antiphlogistic properties.

The new compounds can be prepared by methods which are known inthemselves.

The methods of preparing the compounds include a. Reacting a compound offormula I where R, is hydrogen and R is hydrogen or a lower alkyl groupwith a compound of the formula E-C R 11 where A and R are as definedabove and E is a halogen, especially chlorine or bromine, a hydroxygroup or an acylated hydroxy or reacting with aliphatic lactonescontaining 3-8 carbon atoms, or

b. In a compound of the general formula 1 converting the compound whereR, and/or R are as defined above or R is also another acyl group as iscustomarily used in peptide chemistry is converted to another compoundof formula I by alkylation, acylation, saponification, catalytichydrogenation or reaction with phosphorus pentasulfide or ammonia or alower monoalkylamine having 1-6 carbon atoms, or c. in compounds offormula 111 R III wherein RR; and R are as defined above reducing thenitro group to an amino group and in a given case alkylating the aminogroup formed with a lower alkyl group and/or with a compound of formula11 or acylating with an aliphatic lactone of 3 to 8 carbon atoms.Process (a) Process (a) is suitably carried out in a solvent such as analiphatic alcohol, e.g. methyl alcohol, ethyl alcohol, isopropyl alcoholor butyl alcohol, dioxane tetrahydrofurane, dimethyl sulfoxide ordimethyl formamide at a temperature between 0 and 150C. The process canbe carried out in the presence of basic materials such as pyridine,quinoline, triethylamine, diisopropylamine, potassium carbonate andsodium carbonate, etc. In case E is an acylated hydroxy group,especially preferred acyl groups are those derived from lower saturatedaliphatic carboxylic acids having 2 to 6 carbon atoms, as, for example,the acetyl, hexanoyl and propionyl groups.

In the case where E is a hydroxy group the reaction is undertaken in thepresence of known condensation agents such as dicyclohexylcarbodiimide,diimidazolylcarbonyl l,2-dihydroquinoline or N-ethoxycarbonyl-2-ethoxy-l ,Z-dihydroquinoline.

lf lactones are used in reaction takes place, for example, in inertorganic solvents at temperatures between 250C, in a given case with theuse of conventional condensation agents. Preferably beta or gammalactones are used.

Examples of suitable compounds within formula 11 are acetyl chloride,acetyl bromide, thioacetyl chloride, propionyl chloride, propionylbromide, thiopropionyl bromide, hexanoyl chloride, thiohexanoylchloride, butyryl chloride, octanoyl chloride, chloroacetyl chloride,chloropropionyl chloride, bromoacetyl chloride, acryloyl chloride,acryloyl bromide, 2-chloroacryloyl chloride, methacryloyl chloride,3,3-dimethylacryloyl chloride, methyl chloroformate, ethylchloroformate, hexyl chloroformate, benzoyl chloride, benzoyl bromide,acetic acid, propionic acid, hexanoic acid, aminoacetyl chloride,glycine beta-aminopropionic acid, omegaamino-hexanoic acid,omega-aminoctanoic acid. Process (b) One or two lower alkyl groups areintroduced by alkylation into compounds of formula 1 in which both R,and R are hydrogen or one of these groups is hydrogen. As alkylatingagents there can be used, for example, esters of the formulae R' Hal,ArSO OR' and SO (OR' wherein Hal is a halogen atom (especially chlorine,bromine or iodine), R' is an alkylgroup of l to 6 carbon atoms and Ar isan aromatic group which, for example, can be a phenyl or naphthyl groupwhich in a given case is substituted by one or more lower alkyl groups.Examples are methyl chloride, ethyl bromide,

methyl iodide, ethyl chloride, propyl bromide, isopropyl chloride, butylchloride, butyl bromide, butyl iodide, sec. butyl chloride, sec. butylbromide, t-butyl chloride, sec. butyl bromide, t-butyl chloride, amylchloride, hexyl chloride, heptyl chloride, methyl benzene sulfonate,ethyl benzene sulfonate, alkyl esters of p-toluene sulfonic acid such asmethyl p-toluenesulfonate, ethyl p-toluenesulfonate, propyl p-toluenesulfonate, butyl p-toluene-sulfonate, isobutyl p-toluenesulfonate, hexylp-toluenesulfonate, methyl 2,4- xylenesulfonate, methyl alphanapthalenesulfonate, ethyl beta naphthalene sulfonate, lower dialkylsulfates such as dimethyl sulfate, diethyl sulfate, dipropyl sulfate,dibutyl sulfate and the like. The alkylation can take place, in a givencase with addition of customary acid binding agents such as bases, e.g.sodium hydroxide and potassium hydroxide, alkali carbonates such assodium carbonate and potassium carbonate, alkali hydrides, e.g. sodiumhydride, alkali amides, e.g. sodamine, alkali alcoholates, e.g. sodiummethylate, potassium ethylate, sodium ethylate, sodium octylate, sodiumdecylate, pyridine or other conventional tertiary amines, e.g. dimethylaniline, triethylamine, or tributyl amine at a temperature between 0 andC. in inert solvents such as alcohols, e.g. methyl alcohol, ethylalcohol, propyl alcohol, isopropyl alcohol, butyl alcohol or amylalcohol, dioxane, dimethyl formamide, dimethyl sulfoxide, aromatichydrocarbons such as benzene, toluene or xylene or ketones such asacetone and methyl ethyl ketone (also see LP. and Mary Fieser Reagentsfor Organic Synthesis, John Wiley and Sons, Inc. New York, 1967, Vol 1,pages 1303-4; Vol. 2, page 471 and Vol. 3 (1972) page 349.) Thealkylation can also be carried out to introduce a lower alkyl groupstarting with a compound of formula I in which R, is hydrogen and R isalready present as the stated acyl group or as another easily splittableacyl group or, in a given case, a substituted benzyl group (thealkylation being suitably carried out as given above in the presence ofabase or active alkali compound) and subsequently hydrolyzing off orhydrogenating off the R group by known methods (for example as givenbelow).

As easily splittable groups there can be used, for example, the benzylgroup, a-phenylethyl group, benzyl groups substituted in the benzenenucleus as, for example, the p-bromo or p-nitrobenzyl group, thecarbobenzoxy group, the carbobenzthio group, the trifluoroacetyl group,the phthalyl radical, the trityl radical, the p-toluenesulfonyl radical,the tert. butylcarboxy group and other protective groups used in thesynthesis of peptides (see, for example Jesse. P. Greenstein and MiltonWinitz Chemistry of Amino Acids, John Wiley and Sons, Inc. New York(1961) Vol. 2, pages 883 et seq.) The alkylation of the R, and Rcontaining amino group can also be carried out by reacting a compound offormula 1 where R, and R are hydrogen and the remaining groups R R and Rare as defined above with an aliphatic aldehyde of 1 to 6 carbon atoms,e.g. formaldehyde, acetaldehyde, propionaldehyde, acrolein,butyraldehyde, valeraldehyde, capraldehyde, methacrolein orcrotonaldehyde or an aliphatic ketone with 3 to 6 carbon atoms, e.g.acetone, methyl ethyl ketone, diethyl ketone, or methyl butyl ketone toform the corresponding Schiffs base and simultaneously or subsequentlyhydrogenating. These processes can be carried out at room temperature orelevated temperatures in solvents such as aliphatic alcohols, e.g.methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol orbutyl alcohol, alcohol watermixtures, e.g. 96% ethyl alcohol, dimethylformamide, or dimethyl formamide containing mixtures, etc. For thehydrogenation there can be used, for example, the usual hydrogenationcatalysts such as platium, palladium or nickel with or without carriers.

In the case where R is A ll -C-R A can be exchanged in various ways:Thus, in case A is oxygen, this atom can be replaced by a sulfur atom bymeans of phosphorus pentasulfide. This reaction takes place in inertsolvents such as benzene, toluene, xylene, dioxane, pyridine, quinolineor chlorohydrocarbons, e.g. chlorobenzene at temperatures between and100C. The thus obtained sulfur compound (thioamide), as well as theamides themselves can be reacted in a polar medium with lower alkylamines having 1 to 6 carbon atoms, e.g. methyl amine, ethyl amine,isopropyl amine, butyl amine, amyl amine or hexyl amine or ammoniawhereby compounds are formed of formula 1 in which the group A of the Rradical is an imino or lower alkylimino group. These reactions can becarried out in polar solvents such as methanol, ethanol, isopropanol orexcess amine at temperatures between 0 and 150C.

In case the radical R is the group wherein R is an acylated amino group,this acyl group can be split off by selective saponification. There canbe especially employed easily splittable acyl groups or in a given casesubstituted benzyl groups as are used in peptide chemistry such as thosepointed out supra. This saponification can be carried out, for example,in water, methanol, ethanol, glacial acetic acid or mixtures of these orother solvents which contain the acid or base corresponding to that usedfor hydrolysis (e.g. potassium carbonate, sodium carbonate, alkali, e.g.sodium hydroxide or potassium hydroxide, ammonia, etc.). The temperatureis between 20 and 150C. Various acyl groups, as for example, thecarbobenzoxy radical and the p-tolyloxycarbonyl radical also can besplit off by catalytic hydrogenation in the presence of customaryhydrogenation catalysts, especially palladium catalysts in a solvent orsuspension agent, in a given case under elevated pressure. As solventsor suspension agents there can be used, for example, water, loweraliphatic alcohols, e.g. methyl alcohol, ethyl alcohol or isopropylalcohol, cyclic ethers such as dioxane or tetrahydrofurane, aliphaticethers, e.g. diethyl ether or dipropyl ether, dimethyl formamide, etc.as well as mixtures of these materials. For splitting off there can beused all the methods employed in peptide and aminoacid chemistry for theremoval of protective groups, see the Greenstein et a1. book citedabove. Hydroxy or amino groups which are present can be correspondinglyacylated by the conditions given with process (a) or they can bealkylated as given above.

Process (0) Process (0) is carried out suitably in a solvent such asmethanol, ethanol, isopropanol, dioxane or tetrahydrofurane attemperatures between 0 and 150C. The reduction can be carried out withhydrogen in the presence of metal catalysts such as Raney-nickel,Raneycobalt or noble metal catalysts (palladium, platinum),

in a given case on suitable carriers, et pressure of l to atmosphereabsolute.

lf chemical reduction is employed there can be used nascent hydrogenwith zinc, tin or iron and dilute acids, e.g hydrochloric acid, aluminumamalgam/H O or alkali hydrides or complex metal hydrides such as LiAlH,,LiH, sodium triethoyxy aluminum hydride, sodium dihydrobis(Z-methoxyaluminate) and similar reducing agents or H 5, ammoniumsulfide or alkali sulfides, e.g. sodium sulfide or potassium sulfide.

For the further reaction according to process (c) the solution resultingfrom the reduction can be used directly without previous isolation ofthe amino compound.

Basic compounds of formula 1 can be converted into their salts by knownmethods. As anions for these salts there can be used any of the knownand therapeutically usable acid radicals such as those set forth abovefor example.

If the compounds of formula 1 contain acid groups then these can beconverted in conventional manner into their alkali (e.g. sodium orpotassium), ammonium or substituted ammonium salts. As substitutedammonium salts there may be especially noted salts of tertiary alkylamines, lower aminoalcohols and his and tris (hydroxyalkyl) amines inwhich the alkyl radicals contain l to 6 carbon atoms such astriethylamine, ethanolamine, diethanolamine, triethanolamine,propanolamine, dipropanolamine, trimethylamine, diethyl propyl amine,tributylamine, trihexylamine.

The free bases can be prepared again from the salts of the compounds inthe usual manner, for example, by treating a solution in an organicsolvent such as an alcohol (eg. methanol) with soda or sodium hydroxideor by means of a dilute acid (for example dilute acetic acid).

Those compounds of formula 1 which contain.asymmetric carbon atoms andas a rule result as racemates, can be split into the optically activeisomers in known manner with the help of an optically active acid.However, it is also possible to employ from the beginning an opticallyactive starting material whereby a correspondingly optically active ordiastereomer form is obtained as the end product.

The compounds of the invention are suitable for the production ofpharmaceutical compositions. The pharmaceutical compositions ormedicaments can contain one or more of the compounds of the invention ormixtures of the same with other pharmaceutically active materials. Forthe production of pharmaceutical preparations there can be used thecustomary pharmaceutical carriers and assistants The medicines can beemployed enterally, parenterally, orally or perlingually. For example,dispensing can take place in the form of tablets, capsules, pills,dragees, plugs, salves, jellies, cremes, powders, liquids, dusts oraerosols. As liquids there can be used, for example, oily or aqueous orsuspensions, emulsions, injectable aqueous and oily solutions orsuspensions.

Those starting materials for processes (a), (b) and (c) which are notknown can be prepared in the followmg ways.

A compound of the formula D CH2 3a (v) 3 where Ra is hydrogen or loweralkyl. It is first reacted with an active alkali compound such assodamide, potassium, amide, sodium hydride or finely divided sodium inan inert solvent such as dimethyl formamide, dioxane or benzene and thenthere is chopped in with stirring and in a nitrogen atmosphere thecalculated amount of 2,6-dichloro-3-nitropyridine dissolved in the samesolvent. In many cases it has proven also suitable to change thesequence of addition, for example, to add the alkali compound to asolution of phenylacetic acid or benzyl cyanide derivative and2,6-dichloro-3- nitropyridine. The generally exothermic reaction resultsin the alkali salt of a compound of formula VI.

01$ CH 2 l R Cy 3 where Cy is CN or CO Ra, which salt is coloredstrongly blue or violet. After the end of the reaction this is filteredoff with suction, washed, dissolved in water and treated with dilutedglacial acetic acid until disappearance of the intrinsic color. Thecompound of formula Vl customarily crystallizes out in adequate purity.

As illustrative of this procedure2-[alpha-cyano-)-ochlorobenzyl]-3-nitro-6-chloropyridine was obtained asfollows:

To a solution of grams of o-chlorobenzylcyanide in 1.5 liters of dioxanewith stirring and in a nitrogen atmosphere there were added at 45C. 42grams of sodium hydride (80 percent in white oil). Then the mixture wasstirred for 45 minutes at this temperature. It was then cooled and at 20to 22C.; there were dropped in grams of 2.6-dichloro-3-nitropyridine in500 ml. of dioxane within 30 minutes. Reaction was allowed to continuefor 3 hours at this temperature. The deeply colored sodium salt wasfiltered off with suction, washed with dioxane, dissolved invwater/methanol (1:1 by volume) and dilute acetic acid until change incolor occurred. The desired compound crystallized out, was filtered offwith suction and washed thoroughly with methanol. M.P. 174 to 175C.;Yield R (VII) can be obtained by oxidation. This can be accomplished,for example, with selenium dioxide in dioxane or tetrahydrofurane at 50to C. or it can also be accomplished with 30% hydrogen peroxide solutionat temperatures below 100C, preferably 20 to 50C. in acetone-waterwherein the stoichrometrical amount of an aqueous concentrated KOl-lsolution is dropped in just quick enough that no color disappearancetakes place. In the least procedure the chlorine atom in the 6 positionto a large extent is simultaneously hydrolytically split off. Thereforethere is isolated not only the desired compound but also a compoundanalogous to that of formula Vll where R is 01-1. The latter can beagain chlorinated in known manner with a mixture of PCl /PCl whereby thePCl again deoxygenates the N-oxide simultaneously formed as byproduct.

The nitro group in the compounds of formula Vll is then reduced to theamino group either catalytically (with Pd, Pt, or Raney nickel inalcohols, e.g. methyl alcohol, ethyl alcohol or isopropyl alcohol,dioxane or tetrahydrofurane at 0 to 60C. and at 1 to 50 atmospheresabsolute) or chemically (with LiAlH or Al/Hg/H O, for example, indiethyl ether, dioxane or tetrahydrofurane between 0 to 100C). Thisamino group can then be alkylated with an alkyl group of l to 6 carbonatoms in the manner described previously.

Compounds of formula V111 c (VIII) where R, is F or Br and can beprepared, for example, by heating a compound of formula VI] with asaturated aqueous alcoholic ammonia solution in an autoclave at 100 to120C. for several hours (2 to 4 hours) and then in known mannerdiazotizing the 6-amino-pyridine formed and reacting under theconditions of the Sandmeyer reaction or modified Sandmeyer reaction inthe presence of fluoride or bromide ions and/or the corresponding copper(l) salts (Cu, Br, CuCl) or heating with fluoborate ions. As solventsthere can be used water-alcohol mixture or mixtures of water, dimethylformamide and dimethyl sulfoxide. For the production of fluoroderivatives the dry diazomine fluoborate can also be decomposedthermally.

Compounds of formula VII] in which R, signifies a bromine atom can alsobe prepared by brominating compounds of formula Vlll in which R, is OHby use of a brominating agent such as POBr PBr or SOBr in a given casein an inert solvent, between 20 and 200C. The production of compounds offormula VII] in which R is F can also take place in a modified manner inwhich there is gradually added NaNO to a solution of a compound offormula Vlll where R, signifies amino in concentrated aqueoushydrofluoric acid at a temperature between 0 and 50C., or else a slowstream of nitrous gases is led into such a solution.

The reduction of the nitro group as well as, in a given case, thesubsequent introduction of R, can take place in the manner alreadydescribed.

For example, there are prepared compounds of formula l where R, ischlorine, bromine or fluorine, R and R are in the 0 and/or p-position,where R is chlorine, bromine. flourine, the trifluoromethyl group, thehydroxy group, the methyl group or the methoxy group and R is hydrogenor a radical which is one of those indicated for R R is hydrogen or analkyl group of l to 6 carbon atoms, especially 1 to 3 carbon atoms and Ris hydrogen or an alkanoyl group with 2 to 8 carbon atoms. especially 2to 4 carbon atoms, or an alkanoyl group of 2 to 8 carbon atoms,especially 2 to 4 carbon atoms, which is substituted with l to 3 halogenatoms, especially fluorine or chlorine, preferably in the alpha position(for example a haloacetyl group such as trifluoroacetyl or fluoroacetyl)or an alkanoyl group of 2 to 8 carbon atoms, especially 2 to 4 carbonatoms, substituted with an amino group, or a straight or branched chainalkanoyl group of 3 to 8 carbon atoms, especially 3 to 6 carbon atoms,or a carbalkoxy group of 2 to 8 carbon atoms, especially 2 to 5 carbonatoms (for example, the carbethoxy group, the carbamyloxy group, thecarboctoxy group) or the benzoyl group or :1 benzoyl group substitutedwith halogen atoms or methyl groups: in case R,-, is an alkanoyl groupsubstituted by the amino group or alkylamino group, the amino group ispreferably present in the alpha position (for example the aminoacetylgroup) wherein a hydrogen atom of this amino group can also besubstituted by the carbophenoxy radical. the carbobenzyloxy radical acarbalkoxy radical of 3 to 4 carbon atoms, especially 3 carbon atoms orby an alkanoyl radical of 2 to 4 carbon atoms (for example the acetylradical or the propionyl radical).

Unless otherwise indicated all parts and percentages are by weight.

EXAMPLE 1 Q FQ grams of 2-benzoyl-3-nitro-6-chloropyridine in 500 ml ofdioxane were hydrogenated with 20 grams of Raney nickel at 50atmospheres absolute and 30 to 50C. The filtered hydrogenated solutionwas evaporated in a vacuum and the residue recrystallized once fromethanol. Yield 52 grams. N.P. 160C.

The starting material of example 1 was prepared in the following manner.

To a cooled and stirred solution of 190 grams of2,6-dichloro-3-nitro-pyridine and 117 grams of benzyl cyanide in 2liters of dioxane there was added gradually in a nitrogen atmosphere 64grams of sodium hydride percent in white oil). The reaction mixtureimmediately became colored a deep dark blue, gradually a fine particledprecipitate began to separate out, the temeprature increased (withcooling with ice water) to 30C. After 3 hours there were added about 20ml of ethyl alcohol, stirring continuously for 20 minutes and then themixture filtered with suction. The deep blue sodium salt was dissolvedin 1 liter of water and then treated with dilute acetic acid until thecolor disappeared. The 2-(alpha-cyanobenzyl)-3-nitro-6- chloropyridinecrystallized out in pure form. M.P. 165C.; Yield 146 grams.

A mixture of 200 grams of 2-(alpha-cyanobenzyl)-3-nitro-6-chloropyridine, 5-0 ml of acetone and 160 ml of 30% aqueoushydrogen peroxide solution with stirring were treated dropwise at 3540C. with a concentrated potassium hydroxide solution (made of 75 gramsof KOH and 50 ml of water). The dropwise addition took place just quickenough that a disappearance of color did not take place. Immediatelyafter a disappearance of color remained, which indicated the end of thereaction, the mixture was cooled and the crystalline material whichseparated was filtered off with suction. This material, the amount ofwhich varies between 30 and 40 grams, is2-benzoyl-3-nitro-6-chloropyridine which can be purified throughrecrystallization from methanol. M.P. 106C. The filtrate was acidifiedwith dilute hydrochloric acid, whereupon 2-benzoyl-3-nitro-6-hydroxy-pyridine precipitated out in an amount between and grams, M.P.211C.

This hydroxy compound was likewise converted into the desired2-benzoyl-3-nitro-6-chloropyridine by chlorination. For this purpose 1%grams of 2-benzoyl-3- nitro-6-hydroxypyridine was stirred in a mixtureof 200 ml of phosphorus trichloride, 500 ml. of phosphorus oxychlorideand 190 grams of phosphorus pentachloride for 4 hours at 72C. Then thephosphorus halides were distilled off in a rotary evaporator in avacuum, the residue taken up in 1 liter of chloroform and washed withice water, twice with dilute sodium hydroxide and twice with water. Thechloroform solution was dried, brought to dryness in a vacuum and theresidue recrystallize from methanol. Yield grams; M.P. 106C.

EXAMPLE 2 2-(o-chlorobenzoyl )-3-amino-6-chloropyridine if Cl C l 79grams of 2-(o-chlorobenzoyl)-3-nitro-6- chloropyridine were hydrogenatedin 500 ml of dioxane with 20 grams of Raney nickel at 50 atmospheresabsolute at 30 to 50C., the filtered hydrogenated solution wasevaporated in a vacuum and residue recrystallized once from ethanol.Yield 55 grams; M.P. 170C.

The starting material was made in a manner analogous to that employed inexample 1 but starting from o-chlorobenzyl cyanide.

EXAMPLE 3 C C 11 o 43 grams of 2-benzoyl-3-amino-6-chloropyridine weredissolved in 100 ml of dioxane, then 16 ml of pyridine and finally withstirring 18 ml of propionyl chloride were added. The mixture was stirredfor 2 hours, then water was added crystallization began. The materialwhich precipitated was recrystallized from methanol/water. Yield 48grams; M.P. 140C.

EXAMPLE 4 2-benzoyl-3-( 3,3-dimethyl-acryloylamino )-6- chloropyridine/NH co ca C(CH3)2 20 grams of 2-benzoyl-3amino-6-chloropyridine and 14grams of 3,3-dimethyl acryloyl chloride were stirred for 2 hours in 100ml of dioxane and 9.5 ml of pyridine and then treated with water untilcrystallization'began. The precipitated material was recrystallized frommethanol-water. Yield 23 grams; M.P. 168C.

EXAMPLE 5 2-benzoyl-3carbethoxyamino-6-chloropyridine inn-cooc n 30grams of 2-benzoyl-3amino-6-chloropyridine and 20 grams of ethylchloroformate were stirred for 2 hours in 100 ml of diozane and 20 ml ofpyridine and then treated with water until crystallization began. The

precipitated material was recrystallized from methanolwater. Yield 32grams; M.P. 98C.

EXAMPLE 6 2-benzoyl-3-benzoylamino-6-chloropyridine NH-CO-C H 11.5 gramsof 2-benzoyl-3amino-6-chloropyridine and 7 grams of benzoyl chloridewere stirred for 2 hours in 100 ml of dioxane and 16 ml of pyridine andthen treated with water until crystallization began. The precipitatedmaterial was recrystallized from methanolwater. Yield 11 grams; M.P. 146to 147C.

EXAMPLE 7 2-benzoyl-3-benzyloxycarbonylaminoacetamino-6- chloropyridineEXAMPLE 8 2-benzoyl-3-aminoacetamino-6-chloropyridine UM COCH 111-1 29grams of 2-benzoy1-3-benzyloxycarbonylaminoacetamino-6-chloropyridinewere added in portions to ml of a 30 percent solution of HBr in 99%glacial acetic acid at 5 to 0C. The portions went into solution withstrong development of CO After 15 minutes about 50 ml of dry ether wereadded. The precipitated material was filtered off with suction after 30minutes and washed with ether. Yield 50 grams; M.P. of the hydrobromide250C.

EXAMPLE 9 2-benzoy1-3-(propionyl-methylamino)-6- chloropyridine I CO 13N(CH )C CH CH N CO 47 grams of 2-benzoyl-3-propionylamino-6-chloropyridine (prepared as in example 3) were dissolved in 200 ml ofdimethyl formamide; with stirring and in a nitrogen atmosphere therewere added 5.5 grams of 80% sodium hydride in white oil; after 30minutes there were dropped in 29 ml of methyl iodide and the mixturestirred for 2 hours at 50C. Then there were added 10 ml of methanol andthe mixture evaporated in a vacuum. The compound came out as an oil.

EXAMPLE l0 2-benzoyl-3-methylamino-6-chloropyridine N GO C H 50 grams of2-benzoyl-3-(propionyl-methylamino)- 6-chloro-pyridine were taken up in100 ml of ethanol. 200 ml of water and 200 ml of concentratedhydrochloric acid were added. The mixture was heated at reflux for 10hours and then treated with 1 liter of water. The syrup whichprecipitated crystallized after rubbing for some time. The material wasrecrystallized from ethanol. Yield 24 grams; M.P. 77C.

chloropyridine in 500 ml of dioxane were treated with 26 ml of pyridineand 73 ml of acetyl chloride and stirred for 1 hour. Water was addeduntil turbidity occurred, whereupon the reaction product crystallizedout and this was recrystallized from ethanol. Yield 63 grams; M.P. 132C.

EXAMPLE 122-(o-chlorobenzoyl)-3-benzyloxycarbonylaminoacelamino-6-chloropyridineNH-co-crt -1m-iin? CHE Q 27 grams of benzyloxycarbonyl glycine weresuspended in 200 ml of dry dioxane and 27 grams of PCl added. To thissolution there were added 34 grams of2-(o-chlorobenzoyl)-3-amino-6-chloropyridine and stirred for anotherhour. Subsequently the mixture was treated with ether ether until therewas complete precipitation of the reaction product. Yield 50 grams; M.P.C.

EXAMPLE 13 2-(o-chlorobenzoyl )-3-aminoacetamino-6- chloropyridineEXAMPLE 14 2-(o-fluorobenzoyl )-3-amino-6-chloropyridine 49 grams of2-(o-fluorobenzoyl)-3-nitro-6- chloropyridine were hydrogenated in 500ml of dioxane with addition of 10 grams of Raney nickel at a hydrogenpressure of 40 atmospheres absolute and a temperature of 40 to 60C. Thefiltered hydrogenated solution was concentrated in a vacuum to about 100ml whereupon the reaction product crystallized out. It wasrecrystallized from ethanol. Yield 36 grams; M.P. to 181C.

The starting material was made in a manner analogous to that employed inexample 1 but starting from o-fluorobenzyl cyanide.

The compounds of the invention are suited for the production ofpharmaceutical compositions and preparations. The pharmaceuticalcompositions or drugs contain as the active material one or several ofthe compounds of the invention, in a given case in admixture with otherpharmacologically or pharmaceutically effective materials. Theproduction of the medicine can take place with the use of known andcustomary pharmaceutical carriers and diluents, as well as othercustomary carriers and assistants.

Such carriers and assistants are set forth, for example, in UllmannsEncyklopadie der technischer Chemie, Vol. 4 (1953), pages 1 to 39;Journal of Pharmaceutical Sciences, Vol. 52 (1963). pages 918 et seq; H.v. Czetsch-Lindenwald, Hilfstoffe fur Pharmazie und angrenzende Gebiete;as well as in Pharm. 2nd Vol. 2 (1961) pages 72 et seq.; Dr. H.P.Fiedler, Lexicon der Hilfstoffe fur Pharmazie, Kosmetik und angrenzendeGebiete, Cantor Kg.Aulendorf i. Wurtt, 1971.

Examples of such materials include gelatin, natural sugars such assucrose or lactose, lecithin, pectin, starch (for example corn starch),tylose, talc, lycopodium, silica (for example coloidal silica),cellulose derivatives (for example, cellulose ethers in which thecellulose hydroxy groups partially or completely are etherified withlower alkyl alcohols and/or hydroxyalkyl alcohols, e.g. methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropylcellulose, or methyl hydroxyethyl cellulose), micropulverized cellulose,stearates, e.g. methyl stearate, and glyceryl stearate, magnesium andcalcium salts of fatty acids of 12-22 carbon atoms, e.g. calciumstearate, emulsifiers, fats, oils, especially plantoils (for examplepeanut oil, castor oil, olive, oil, sesame oil, cotton seed oil, cornoil, mono-, diand triglycerides of saturated fatty acids having 12 to 18carbon atoms and their mixtures, e.g. glycerol tristearate, glyceroltripalmitate, glycerol trilaurate, glycerol distearate, glycerolmonostearate, pharmaceutically compatible monoand polyvalent alcoholsand polyglycols such as glycerine, mannitol, sorbitol, pentaerythritol,ethyl alcohol, diethylene glycol, triethylene glycol, ethylene glycol,propylene glycol, dipropylene glycol, polyethylene glycol 400, as wellas derivatives of such alcohols and polyglycols, dimethyl sulfoxide,esters of saturated and unsaturated fatty acids (2 to 22 carbon atoms,especially 10 to 18 carbon atoms) with monovalent alcohols l to 20carbon atoms) such as ethyl alcohol, methyl alcohol, octadecylalcohol,eicosanyl alcohol or polyhydric alcohols such as glycols,glycerine, diethylene glycol, pentaearythritol, sorbitol, mannitol,etc., e.g. glycerol stearate, glyceryl palmitate, pentaerythritolstearate, ethylene glycol stearate; such esters of polyvalent alcoholscan in a given case also be etherified, benzyl benzoate, dioxolane,glycerine formal, glycol furfural, dimethyl acetamide, lactamide,lactates, e.g., ethyl lactate, ethyl carbonate, silicones (especiallymedium viscosity dimethyl polysiloxane) etc.

For production of solutions there can be used, for example, water orphysiologically compatible organic solvents as, for example, ethanol,1,2-propylene glycol, polyglycols, e.g. triethylene glycol, and theirderivatives, dimethyl sulfoxide, fatty alcohols, e.g. lauryl alcohol,octadecyl alcohol and oleyl alcohol, triglycerides, partial esters ofglycerine, paraffins, etc.

For the production of the preparations there can be used theconventional solvent aids. As solvent aids there can be used, forexample,polyoxyethylated fats, polyoxyethylated oletriglycerides,linoleized oletriglycerides. Examples of oletriglycerides are olive oil,peanut oil, castor oil, sesame seed oil, cotton seed oil, corn oil (seealso Dr. H.P. Fiedler, Lexikon der Hilfstoffe fur Pharmazie, Kosmetikund angrenzende Gebiete 1971, pages 191 to 195). By the termpolyoxyethylated is meant those materials where the polyoxyethylenechain contains 2to 40, and especially 10 to 20, ethylene oxide units.Such polyoxyethylated materials can be obtained, for example, byreacting the corresponding glyceride with ethylene oxide (for example 40moles of ethylene oxide per mole of glyceride).

Furthermore there can be added preservatives, stabilizers, buffers,taste correctives, antioxidants and complex formers (for exampleethylenediaminotetraacetic acid) and the like. In a given case forstabilization of the active molecule a pH range of about 3-7 can beestablished with physiologically compatible acids or buffers. Generallya neutral to weakly acid (to pH 5) pH value is preferred.

As antioxidants there can be used, for example, sodium meta bisulfite,ascorbic acid, gallic acid, alkyl gallates, e.g. methyl gallate, ethylgallate and propyl gallate, butylated hydroxyanisole,nordihydroguairatic acid, tocopherol (aiphatocopherol) as well astocopherol and synergists (as for example lecthin, ascorbic acid orophosphoric acid). The addition of the synergist considerably increasesthe antioxidant activity of tocopherol.

As preservatives there can be used, for example, sorbic acid,p-hydroxybenzoic acid esters (for example lower alkyl esters such asmethyl p-hydroxybenzoate and ethyl p-hydroxybenzoate), benzoic acid,sodium benzoate, trichloroisobutyl alcohol, phenol, cresol, benzethoniumchloride and formatin derivatives.

The pharmacological and galenical treatment of the compounds of theinvention takes place according to the usual standard methods. Forexample, the active material or materials and the assistant or carriermaterial are well mixed by homogenizing or stirring (for example bymeans ofa colloid mill or ball mill). Temperatures between 20 and C.,preferably 20 to 50C. are employed.

The drugs can be used orally, parenterally, rectally,

vaginally, perlingerally or topically or as sprays, e.g. in aerosols.

The addition of other medicinally active materials is also possible ordesirable.

The compounds of the invention in combat tests and carrageenin edematests show good sedative, psychosedative, anxiolytic and antiphlogisitcactivity.

This activity is comparable with the activity of the known medicineDiazepam.

The lowest effective dosages in animal experiments, for example, are:

2 mg/kg body weight orally 1 mg/kg sublingually 0.5 mg/kg intravenouslyAs a general range of dosage for anxiolytic activity (based on animalstudies) there can be employed:

2-100 mg/kg body weight orally l-50 mg/kg sublingually 0.5-20 mg/kgintravenously The compounds of the invention have utility in treatingirritation, tension, anxiety, increased irritability, psychoneuroticdisturbances of children. Vegetative dystony, psychosomatic disturbancesand organic neuoroses. Sleep disturbances, muscular spasms (also inillnesses of the rheumatic cycle). Treatment of cramps.

For facilitating birth, abortus imminens, threatened or initiated earlybirth or miscarriage, placenta praevia. Preparation for operation.

The pharmacuetical preparations generally contain either 1 or 2 of theactive components of the invention.

The compounds can be delivered in the form of tablets, capsules, pills,dragees, suppositories, gels, cremes, powders, liquids, dusts oraerosols. As liquids there can be used oily or aqueous solutions orsuspensions or emulsions. The preferred forms of use are tablets whichcontain between 2 and 50 mg of active material or solutions whichcontain between 0.1 and l percent of active material.

In individual doses the amount of active component of the invention canbe used, for example, in an amount of 2-10 mg dispensed orally or 0.5 mgdispensed parenterally (for example intravenously or intramuscularly).

When used rectally or vaginally there is employed between 1 and mg.

There is no specific dosage for inhalation (as solution or aerosol) orfor local application to the skin or mucous membrane (for example in theform of solutions. lotions. emulsions. salves. etc.)

The dosages set forth are always calculated as the free base.

For example. there is recommended the use of l to 2 tablets containing 2to 10 mg of active ingredient 3 times daily or for intravenous injection1 to 3 times a day a l to 2 ml ampoule containing 0.5 to 10 mg of activematerial is recommended. ln oral application the minimum daily dosageis. for example. 2 mg. the maximum daily dosage should not be over 50mg.

For the treatment ofdogs and cats the individual oral dosage generallyis between about 2 and mg/kg of body weight; the parenteral dosagebetween approximately 0.5 and 1.0 mg/kg of body weight.

For the treatment of horses and cattle the oral dosage is generallybetween about Zand 20 mg/kg; the parenteral individual dosage is betweenabout 0.5 and l0 mg/kg of body weight.

The acute toxicity of the compounds ofthe invention in the mouse(expressed by the LD 50 mg/kg method of Millar and Tainter. Proc. Soc.Exph. Biol. and Med.. Vol. 57 (1944) pages 251 et seq. in oralapplication is between 500 and 3.000 mg/kg (or above 500 mg/kg).

The drugs can be used in human medicine, in veterinary medicine. e.g..to treat cats. dogs. horses. sheep. cattle. goats and pigs or inagriculture. The drugs can be used alone or in admixture with otherpharmacologically active materials.

The salts. e.g. the hydrochloride salts. are also useful as curingagents for melamine formaldehyde resins.

What is claimed is:

l. A pyridine compound of the formula 18 TU R N/ 5 l 1 \N R where R ishalogen. R is hydrogen. halogen. trifluoromethyl, hydroxy. cyano. loweralkyl or lower alkoxy. R is hydrogen. halogen. hydroxy or lower alkyl.R. is hydrogen or lower alkyl and R is hydrogen or lower alkyl or apharmacologically acceptable salt thereof.

2. A pyridine compound according to claim 1 wherein R is halogen ofatomic weight 9 to 80. R is hydrogen. halogen of atomic weight 9 to 80.trifluoromethyl. hydroxy. cyano. alkyl of l to 6 carbon atoms or alkoxyof l to 6 carbon atoms. R;; is hydrogen. halogen of atomic weight 9 to80. hydroxy or alkyl of l to 6 carbon atoms. R. is hydrogen or alkyl of1 to 6 carbon atoms and R is hydrogen or alkyl of l to 6 atoms.

3. A pyridine compound according to claim 2 wherein R is chlorine.

4. A pyridine compound according to claim 3 wherein R is hydrogen and Ris hydrogen or alkyl of l to 4 carbon atoms.

5. A pyridine compound according wherein R is hydrogen.

6. A pyridine compound according to claim 5 wherein R is hydrogen.chlorine. fluorine. trifluoromethyl or alkyl of l to 4 carbon atoms.

7. A compound according to claim 5 wherein R is hydrogen or halogen ofatomic weight 9 to 80.

8. A pyridine compound according to claim 4 wherein R is hydrogen.

9. A pyridine compound according to claim 8 wherein R is hydrogen.chlorine or fluorine.

10. A pyridine compound according to claim 9 which isZ-benzoyl-3-amino-o-chloropyridine.

11. A compound according to claim 9 which isZ-(ochlorobenzoylJ-3-amino-o-chloropyridine.

to claim 4

1. A PYRIDINE COMPOUND OF THE FORMULA
 2. A pyridine compound accordingto claim 1 wherein R1 is halogen of atomic weight 9 to 80, R2 ishydrogen, halogen of atomic weight 9 to 80, trifluoromethyl, hydroxy,cyano, alkyl of 1 to 6 carbon atoms or alkoxy of 1 to 6 carbon atoms, R3is hydrogen, halogen of atomic weight 9 to 80, hydroxy or alkyl of 1 to6 carbon atoms, R4 is hydrogen or alkyl of 1 to 6 carbon atoms and R5 ishydrogen or alkyl of 1 to 6 atoms.
 3. A pyridine compound according toclaim 2 wherein R1 is chlorine.
 4. A pyridine compound according toclaim 3 wherein R4 is hydrogen and R5 is hydrogen or alkyl of 1 to 4carbon atoms.
 5. A pyridine compound according to claim 4 wherein R3 ishydrogen.
 6. A pyridine compound according to claim 5 wherein R2 ishydrogen, chlorine, fluorine, trifluoromethyl or alkyl of 1 to 4 carbonatoms.
 7. A compound according to claim 5 wherein R2 is hydrogen orhalogen of atomic weight 9 to
 80. 8. A pyridine compound according toclaim 4 wherein R5 is hydrogen.
 9. A pyridine compound according toclaim 8 wherein R2 is hydrogen, chlorine or fluorine.
 10. A pyridinecompound according to claim 9 which is2-benzoyl-3-amino-6-chloropyridine.
 11. A compound according to claim 9which is 2-(o-chlorobenzoyl)-3-amino-6-chloropyridine.